The long-term objective of this proposal is to gain insight into the cellular and subcellular mechanisms involved in neuroimmunomodulation. Since some of the neurotransmitters and neuropeptides that modulate the immune response are known modulators of ion channel activity in excitable cells, it seems reasonable to assume that modulation of ion channels in cells of the immune system is an essential feature of neuroimmunomodulation. Therefore, in this proposal patch clamp methods will be used to monitor ion channel activity in murine spleen T lymphocytes and its modulation by neurotransmitters and neuropeptides. Cholinergic and beta-adrenergic agonists, and substance P will be tested since receptors for these agents in lymphocytes have been described. The extent of modulation by these agents in resting or proliferating T cells will be assessed to determine which ones are more susceptible to modulation of their ionic currents. To determine the second messenger system involved in transmembrane signaling, these systems will be altered using extracellular and/or intracellular agents so as to mimic the observed response to T cells to a particular modulator. Ion channels are required for many events in T cell activation. Modulation of T cell ion channel properties by biologically active molecules may allow these cells to alter cellular behavior on a long-term basis and, thus, play an essential role in neuroimmunomodulation.